title: Identification of the primary mechanism of complement evasion by the periodontal pathogen, Treponema denticola.
abstract: Treponema denticola, a periodontal pathogen, binds the complement regulatory protein Factor H (FH). Factor H binding protein B (FhbB) is the sole FH binding protein produced by T. denticola. The interaction of FhbB with FH is unique in that FH is bound to the cell and then cleaved by the T. denticola protease, dentilisin. A ∼ 50-kDa product generated by dentilisin cleavage is retained at the cell surface. Until this study, a direct role for the FhbB-FH interaction in complement evasion and serum sensitivity had not been demonstrated. Here we assess the serum resistance of T. denticola strain 35405 (Td35405wt) and isogenic mutants deficient in dentilisin (Td35405-CCE) and FhbB production (Td35405ΔfhbB), respectively. Both dentilisin and FhbB have been postulated to be key virulence factors that mediate complement evasion. Consistent with conditions in the subgingival crevice, an environment with a significant concentration of complement, Td35405wt was resistant to serum concentrations as high as 25%. Deletion of fhbB (Td35405ΔfhbB), which resulted in the complete loss of FH binding ability, but not inactivation of dentilisin activity (Td35405-CCE), rendered T. denticola highly sensitive to 25% human serum with 80% of the cells being disrupted after 4 h of incubation. Heat treatment of the serum to inactivate complement confirmed that killing was mediated by complement. These results indicate that the FH-FhbB interaction is required for serum resistance whereas dentilisin is not. This report provides new insight into the novel complement evasion mechanisms of T. denticola.
authors.affiliation: Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: McDowell
authors.forename: J
authors.initials: J
authors.lastname: Frederick
authors.forename: D P
authors.initials: DP
authors.lastname: Miller
authors.forename: M P
authors.initials: MP
authors.lastname: Goetting-Minesky
authors.forename: H
authors.initials: H
authors.lastname: Goodman
authors.forename: J C
authors.initials: JC
authors.lastname: Fenno
authors.forename: R T
authors.initials: RT
authors.lastname: Marconi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001431:Bacteriological Techniques; D001770:Blood Bactericidal Activity / Q000235:genetics / Q000276:immunology; D002918:Chymotrypsin / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H / Q000276:immunology* / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000276:immunology* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007106:Immune Sera / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology; D051379:Mice; D010447:Peptide Hydrolases; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion / Q000235:genetics; D048373:Treponema denticola / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D051056:Complement Inactivating Agents; D007106:Immune Sera; D007155:Immunologic Factors; D037521:Virulence Factors; D017242:Complement Factor H; D010447:Peptide Hydrolases; C102570:dentilisin; D002918:Chymotrypsin